Thioureido-cyclodextrins, utilized in particular to solubilize anti-tumor, and antiparasitic agents and their preparation processes

Abstract

The invention relates to thioureido-cyclodextrins, usable in particular to solubilize anti-tumor and antiparasitic agents and their preparation processes. These thioureido-cyclodextrins correspond to the formula: ##STR1## with m=6, 7 or 8, R 1 represents OH or NH--CS--NHR 2 , at least one of the R 1 being NH--CS--NHR 2 , R 2 represents an alkyl, monosaccharide, oligosaccharide glycosyl-amino acid or glycopeptide group. These cyclodextrins are usable for solubilizing anti-tumor or antiparasitic agents of the Taxol family.

What is claimed is: 
     
       1. Thioureido-cyclodextrin corresponding to the formula: ##STR9## in which m is equal to 6, 7 or 8 and where the R 1 , which may be identical or different, represent OH or NH--CS--NHR 2  with R 2  representing an alkyl group, a substituted or unsubstituted monosaccharide group or a substituted or unsubstituted oligosaccharide group, a glycosyl-amino acid group or a glycopeptide group, provided that at least one of the R 1  represents NH--CS--NHR 2 . 
     
     
       2. Thioureido-cyclodextrin according to claim 1, wherein all R 1  represent --NH--CS--NH--R 2 . 
     
     
       3. Thioureido-cyclodextrin according to claim 1, wherein one R 1  group represents --NH--CS--NHR 2  and the remaining R 1  groups are OH. 
     
     
       4. Thioureido-cyclodextrin according to claim 3, wherein R 2  is a methyl group. 
     
     
       5. Thioureido-cyclodextrin according to claim 2, wherein R 2  is a methyl-α-D-glucopyranosid-6-yle group. 
     
     
       6. Thioureido-cyclodextrin according to claim 3, wherein R 2  is a methyl-2,3,4-tri-0-acetyl-α-D-glucopyranosid-6-yle group. 
     
     
       7. Thioureido-cyclodextrin according to claim 3, wherein R 2  is a N-glycyl-β-D-glucopyranosylamin-6-yle group. 
     
     
       8. Preparation process of thioureido-cyclodextrin corresponding to the formula: ##STR10## in which m is equal to 6, 7 or 8 and where the R 1 , which may be identical or different, represent OH or NH--CS--NHR 2  with R 2  representing an alkyl group, a substituted or unsubstituted monosaccharide group or a substituted or unsubstituted oligosaccharide group, a glycosyl-amino acid group or a glycopeptide group, provided that at least one of the R 1  represents NH--CS--NHR 2 , comprising reacting an isocyanato cyclodextrin of formula: ##STR11## in which the R 3 , which may be identical or different, represent OH or NCS, and where n is equal to 5, 6 or 7, with an amine of formula R 2  --NH 2  . 
     
     
       9. Preparation process of thioureido-cyclodextrin of formula: ##STR12## in which m is equal to 6, 7 or 8 and where the R 1 , which may be identical or different represent OH or NH--CS--NHR 2  where R 2  represents an alkyl group, a substituted or unsubstituted monosaccharide group or a substituted or unsubstituted oligosaccharide group, a glycosyl-amino acid group or a glycopeptide group, provided that at least one of the R 1  represents NH--CS--NHR 2 , comprising reacting an amino-cyclodextrin of formula: ##STR13## in which the R 4 , which may be identical or different, represent OH or NH2, and where n is equal to 5, 6 or 7, with an isothiocyanate of formula R 2  --NCS. 
     
     
       10. An inclusion complex of a thioureido-cyclodextrin represented by the formula: ##STR14## wherein m is equal to 6, 7 or 8; each R 1 , independently, represents OH or NH--CS--NHR 2 , wherein R 2  represents an alkyl group, a substituted or unsubstituted monosaccharide group or a substituted or unsubstituted oligosaccharide group, a glycosyl-amino acid group or a glycopeptide group, provided at least one R 1  represents NH--CS--NHR 2 , with a pharmaceutically active molecule.   
     
     
       11. A complex according to claim 10, wherein the pharmacologically active molecule is an anti-tumor or antiparasitic agent. 
     
     
       12. A complex according to claim 11, wherein the anti-tumor or antiparasitic agent belongs to the Taxol family. 
     
     
       13. A pharmaceutical composition comprising an inclusion complex of a thioureido-cyclodextrin according to claim 10, with a pharmacologically accepted vector. 
     
     
       14. A pharmaceutical composition according to claim 13, in the form of an aqueous solution. 
     
     
       15. A pharmaceutical composition according to claim 13, wherein the pharmacologically active molecule is an anti-tumor or antiparasitic agent. 
     
     
       16. A pharmaceutical composition according to claim 15, wherein the anti-tumor or antiparasitic agent belongs to the Taxol family. 
     
     
       17. A pharmaceutical composition according to claim 16, wherein one of the R 1  represents NHCSNHR 2 , the other R 1  represent OH, R 2  is a methyl group, and m is equal to 7.